A single, maximal tolerated dose of the organophosphate insecticide chlorpyrifos (CPF, 279 mg/kg, sc) caused extensive inhibition of striatal and cortical cholinesterase (ChE) activity in adult rats at two (94-96%), four (64-74%) and six (36-38%) weeks after treatment. These persistent changes in ChE activity were concomitant with significant reductions in striatal muscarinic receptor (3H quinuclidinyl benzilate) binding sites (50, 31 and 18% reduction in B max at 2, 4 and 6 weeks after exposure) and a slight but significant alteration in the apparent affinity constant, K(D), at 2 and 4 weeks after treatment. Neither ChE activity nor muscarinic receptor binding were different from control levels at 12 weeks after exposure. CPF treatment caused a significant reduction in motor activity for the first two days after treatment, after which basal activity levels were not different from controls. These data indicate that a single, acute exposure to CPF in adult rats can cause long-term neurobehavioral/neuropharmacological changes which may persist following the recovery of neurochemical parameters generally associated with OP exposure and/or tolerance.